Physiological characteristics of malignant tumors such as blood flow and vascular permeability are strongly coupled to therapeutic effects. Tomographic vascular dynamic information is of enormous utility in monitoring tumor growth and vessel recruitment, as well as in assessing the therapeutic response of novel chemotherapeutic agents. We propose to develop a real-time tomosynthesis (TS) system to image vascular dynamics by integrating novel stationary x-ray source array technology with an existing flat-panel detector. The system will be suitable for vascular studies in modestly sized objects such as human breasts or small animals, particularly mice and rats because they are widely used for models of human diseases, including cancer. The dynamic imaging system will provide time-resolved tomographic images. After we design, fabricate, and qualify the system, we will evaluate it using phantoms to acquire real-time tomographic image data sets. These data sets will provide important information to guide the further engineering development of the stationary x-ray source technology and real-time TS system. The specific aims of this R21 proposal are to: Aim 1. Construct a real-time multi-source tomographic imaging system for vascular analysis (Year 1) Aim 2. Demonstrate stationary source operation and quantify system temporal and spatial performance using phantoms and state-of-the-art image assessment techniques. (Year 2) The stationary x-ray source proposed for demonstration in this proposal could significantly impact other areas of medical imaging technology. The potential for increased imaging speed and the implementation of novel acquisition geometries imparted by such sources could lead to the development of compact, affordable CT and digital TS systems for use in hospitals, clinics, rural areas, and laboratories, and thereby benefit both the medical care and research fields. PUBLIC HEALTH RELEVANCE: We propose to significantly improve medical imaging technology by developing an x-ray imaging system that will allow cancer researchers to take three-dimensional x-ray motion pictures. The potential for increased imaging speed, reduced system cost, and the implementation of novel acquisition geometries imparted by such a device could lead to the development of compact, affordable CT and digital tomosynthesis systems for use in hospitals, clinics, rural areas, and laboratories, and thereby benefit both the medical care and research fields.